Hemorrhagic vasculitis in children

Henoch-Schonlein disease (hemorrhagic vasculitis, anaphylactoid purpura, hemorrhagic vasculitis, allergic purpura, Henoch's hemorrhagic purpura, capillary toxicosis) is a common systemic disease with predominant damage to the microcirculatory bed of the skin, joints, gastrointestinal tract, and kidneys. The most vulnerable part of the terminal vascular bed are postcapillary venules; capillaries are in second place in terms of damage, and arterioles are in third place. The microcirculatory bed of various organs, including the skin, is affected.

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Epidemiology

The incidence of hemorrhagic vasculitis is 23-25 per 10,000 population; children aged 4 to 7 years are most often affected, boys are slightly more often.

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Causes hemorrhagic vasculitis in children.

The causes of hemorrhagic vasculitis remain unclear. Some authors associate hemorrhagic vasculitis with various infections, while others attach greater importance to the allergic predisposition of the body, which in the presence of chronic foci of infection (chronic tonsillitis, caries, tuberculosis infection, etc.) leads to a decrease in immunity. Hemorrhagic vasculitis is a hyperergic vascular reaction to various factors, most often infectious (streptococcus and other bacteria, viruses, mycoplasma). In some cases, the development of the disease is preceded by vaccination, food and drug allergens, insect bites, trauma, cooling, etc. The onset of the disease is often preceded by a viral or bacterial infection. Allergic reactions in the anamnesis, mainly in the form of food allergy or drug intolerance, are much less common. The role of hereditary factors is not excluded, for example, a connection with HLA B35 has been noted.

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Pathogenesis

The following factors are important in the pathogenesis of hemorrhagic vasculitis: hyperproduction of immune complexes, activation of the complement system, increased vascular permeability, damage to the vascular endothelium, and hypercoagulation. The basis of vascular damage in this disease is generalized vasculitis of small vessels (arterioles, venules, capillaries), characterized by perivascular infiltration by granulocytes, endothelial changes, and microthrombosis. In the skin, these lesions are limited to the vessels of the dermis, but extravasates reach the epidermis. In the gastrointestinal tract, there may be edema and submucosal hemorrhages, and erosive and ulcerative lesions of the mucous membrane are also possible. In the kidneys, segmental glomerulitis and capillary occlusion by fibrinoid masses are noted; older lesions are characterized by the deposition of hyaline material and fibrosis. As a result, aseptic inflammation develops in the microvessels with destruction of the wall, an increase in its permeability, the hypercoagulation mechanism is triggered, the rheological properties of the blood deteriorate, depletion of the anticoagulant link of the blood coagulation system is possible, free radical stress is observed, which leads to tissue ischemia.

Pathology of hemorrhagic vasculitis (Schonlein-Henoch disease)

In the skin, changes are localized mainly in small vessels of the dermis in the form of leukoclastic vasculitis with extravasations of erythrocytes into the surrounding tissue. In capillaries and other vessels, destructive changes in the walls of the fibrinoid necrosis type often develop. Fibrinoid changes are also observed in the collagen fibers surrounding the vessels. Sometimes necrosis of the vascular walls and surrounding collagen occurs, which leads to closure of the lumen of the vessel. Perivascular infiltrate is observed, but infiltration of the vessel walls often occurs, consisting mainly of neutrophilic granulocytes and lymphocytes. Karyorrhexis, or leukoclasia, with the formation of "nuclear dust" is characteristic. In some cases, diffuse infiltration of the upper parts of the dermis is determined against the background of pronounced edema and fibrinoid swelling with extravasations of erythrocytes. In such cases, the epidermis also undergoes necrosis with the formation of ulcerative defects.

In chronic cases, necrobiotic changes and extravasations of erythrocytes are less pronounced. The capillary walls are thickened, sometimes hyalinized, the infiltrate consists mainly of lymphocytes with an admixture of a small number of neutrophilic and eosinophilic granulocytes. As a rule, karyorrhexis is detected, which is an expression of the anaphylactoid state. As a result of further changes in erythrocytes and their phagocytosis by macrophages, hemosiderin granules are found in them.

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Histogenesis of hemorrhagic vasculitis (Schonlein-Henoch disease)

The disease is based on the deposition of IgA in the walls of skin vessels and renal glomeruli. Fibrinogen and complement component C3 are often also detected. Increased levels of IgA and IgE are detected in the patients' serum. Electron microscopic and immunological studies have revealed that adaptive changes initially occur in the endothelial cells of the affected capillaries: mitochondrial hypertrophy, intense pinocytosis, an increase in the number of lysosomes and active cytoplasmic transport, even phagocytosis. The presence of immune complexes in the vascular lumens causes platelet aggregation on the endothelial surface and their migration through the wall. At the same time, platelets are damaged and secrete vasoactive substances. Subsequently, neutrophilic granulocytes and tissue basophils, which secrete vasoactive substances, increase the damage to the vascular walls of the infiltrate cell.

Symptoms hemorrhagic vasculitis in children.

Hemorrhagic vasculitis usually begins acutely, with subfebrile, less often febrile increase in body temperature, and sometimes without a temperature reaction. The clinical picture can be represented by one or several of the characteristic syndromes (cutaneous, articular, abdominal, renal), depending on which simple and mixed forms of the disease are distinguished.

Skin syndrome (purpura) is found in all patients. Most often at the onset of the disease, sometimes following the abdominal or other characteristic syndrome, a symmetrical small-spotted or maculopapular hemorrhagic rash appears on the skin of the extensor surfaces of the limbs, mainly the lower ones, on the buttocks, around large joints. The intensity of the rash varies - from single elements to abundant, confluent, sometimes in combination with angioedema. The rash is wave-like, recurrent. In most cases, hemorrhagic vasculitis begins with typical skin rashes - small-spotted, symmetrically located elements similar to bruises that do not disappear when pressed. Rashes on the skin of the face, trunk, palms and feet are less common. When the rash fades, pigmentation remains, in place of which peeling appears with frequent relapses.

Joint syndrome is the second most common symptom of hemorrhagic vasculitis. The degree of joint damage varies from arthralgia to reversible arthritis. Large joints are predominantly affected, especially knee and ankle joints. Pain, swelling, and changes in the shape of the joints appear, which last from several hours to several days. There is no persistent deformation of the joints with impairment of their function.

Abdominal syndrome caused by edema and hemorrhages in the intestinal wall, mesentery or peritoneum is observed in almost 70% of children. Patients may complain of moderate abdominal pain that is not accompanied by dyspeptic disorders, does not cause much suffering and passes on its own or in the first 2-3 days from the start of treatment. However, severe abdominal pain is often paroxysmal, occurs suddenly like colic, has no clear localization and lasts for several days. There may be nausea, vomiting, unstable stool, episodes of intestinal and gastric bleeding. The presence of abdominal syndrome from the onset of the disease, the recurrent nature of the pain require joint observation of the patient by a pediatrician and a surgeon, since pain syndrome in hemorrhagic vasculitis can be caused by both the manifestation of the disease and its complication (intussusception, intestinal perforation).

Renal syndrome is less common (40-60%) and in most cases does not occur first. It manifests itself as hematuria of varying severity, less often - the development of glomerulonephritis (Schonlein-Henoch nephritis), mainly hematuric, but possibly nephrotic form (with hematuria). Glomerulonephritis is morphologically characterized by focal mesangial proliferation with deposition of immune complexes containing IgA, as well as the C3 component of complement and fibrin. Sometimes diffuse mesangiocapillary glomerulonephritis is observed, in severe cases combined with extracapillary crescents. With age, the frequency of kidney damage increases. The leading symptom of hemorrhagic vasculitis is moderate hematuria, usually combined with moderate proteinuria (less than 1 g / day). In acute cases, macrohematuria may occur at the onset of the disease, which has no prognostic value. Glomerulonephritis often occurs in the first year of the disease, less often - during one of the relapses or after the disappearance of extrarenal manifestations of hemorrhagic vasculitis.

The course of hemorrhagic vasculitis is cyclical: a clearly defined debut 1-3 weeks after an acute viral or bacterial infection, vaccination and other causes, and recovery after 4-8 weeks. Isolated observations of hemorrhagic vasculitis in children, which proceeds extremely severely in the form of fulminant purpura, are described.

Often the course becomes wave-like with repeated rashes (as a monosyndrome or in combination with other syndromes), recurring over 6 months, rarely 1 year or more. As a rule, repeated waves of rashes in the presence of abdominal syndrome are accompanied by the appearance of renal syndrome.

Chronic course is typical for variants with Schonlein-Henoch nephritis or with isolated continuously recurring cutaneous hemorrhagic syndrome.

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Forms

There is no accepted classification. In working classifications of Henoch-Schonlein disease, the following are distinguished:

• phase of the disease (initial period, relapse, remission);
• clinical form (simple, mixed, mixed with kidney damage);
• main clinical syndromes (skin, joint, abdominal, renal);
• severity (mild, moderate, severe);
• nature of the course (acute, protracted, chronic recurrent).

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Diagnostics hemorrhagic vasculitis in children.

The diagnosis of hemorrhagic vasculitis is established by the nature of the acutely developed skin syndrome, primarily by the presence of symmetrically located small-spotted hemorrhagic rash on the lower extremities. Difficulties arise if the first manifestation of the disease is pain in the joints, abdomen or changes in urine tests. In these cases, diagnosis is possible only with the subsequent appearance of a typical rash.

Laboratory diagnostics of hemorrhagic vasculitis

In a typical picture of hemorrhagic vasculitis, the peripheral blood analysis may show moderate leukocytosis with neutrophilia, eosinophilia, and thrombocytosis. In the absence of intestinal bleeding, the hemoglobin level and the number of erythrocytes are normal.

General urine analysis is altered in the presence of nephritis; transient changes in urinary sediment are possible.

The blood coagulation system in hemorrhagic vasculitis is characterized by a tendency to hypercoagulation, therefore, the hemostasis state should be determined initially and subsequently to control the adequacy of therapy. Hypercoagulation is most pronounced in severe cases. To determine the hemostasis state and the effectiveness of the prescribed treatment, the level of fibrinogen, soluble fibrin-monomer complexes, thrombin-antithrombin III complex, D-dimers, prothrombin fragment F _w and fibrinolytic activity of the blood should be monitored.

The wave-like course of hemorrhagic vasculitis, the appearance of nephritis symptoms are the basis for determining the immune status, identifying a persistent viral or bacterial infection. As a rule, children with hemorrhagic vasculitis have increased concentrations of C-reactive protein, IgA in the blood serum. Immunological changes in the form of increased levels of IgA, CIC and cryoglobulins often accompany recurrent forms and nephritis.

A biochemical blood test has practical significance; only in cases of kidney damage can changes in the level of nitrogenous waste and potassium in the blood serum be detected.

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Instrumental methods for hemorrhagic vasculitis

According to indications, ECG, chest X-ray, ultrasound of abdominal organs are prescribed. The appearance of signs of kidney damage is the basis for ultrasound of the kidneys, dynamic nephroscintigraphy, since these children often have abnormalities in the development of the urinary system, signs of renal dysembryogenesis, and impaired storage and excretory functions of the kidneys. These results allow us to predict the course of nephritis in Henoch-Schonlein disease, monitor treatment, persistence of glomerulonephritis manifestations, despite the therapy, is an indication for kidney biopsy.

Differential diagnosis

Differential diagnosis of hemorrhagic vasculitis should be carried out primarily with diseases that are characterized by hemorrhagic purpura: infections (infective endocarditis, meningococcemia), other rheumatic diseases, chronic active hepatitis, tumors, lymphoproliferative diseases, many of these diseases occur with damage to the joints and kidneys.

The presence of a small (petechial) rash may raise suspicion of thrombocytopenic purpura, but Henoch-Schonlein disease is characterized by a typical localization of the rash (on the buttocks, lower extremities), and there is no thrombocytopenia.

Abdominal syndrome in hemorrhagic vasculitis should be distinguished from diseases accompanied by a picture of acute abdomen, including acute appendicitis, intestinal obstruction, perforated gastric ulcer, yersiniosis, nonspecific ulcerative colitis. In favor of Schonlein-Henoch disease are cramping pains, at the height of which bloody vomiting and melena appear, and accompanying skin changes, articular syndrome. With the predominance of gastrointestinal symptoms, the clinical picture may resemble the picture of acute abdomen, therefore, when examining each patient with acute abdominal pain, one should remember about hemorrhagic vasculitis and look for accompanying rashes, nephritis or arthritis.

In severe kidney damage, acute glomerulonephritis may be suspected; identification of other manifestations of hemorrhagic vasculitis helps in differential diagnosis. If the patient suffers from chronic kidney disease, it is necessary to find out whether he or she has had hemorrhagic vasculitis in the past. Renal forms of the disease should be differentiated primarily from IgA nephropathy, which occurs with relapses of macrohematuria or microhematuria.

Differential diagnostics with other rheumatic diseases rarely causes difficulties. An exception is systemic lupus erythematosus, which at the onset may have symptoms of hemorrhagic vasculitis, but at the same time, immunological markers (antibodies to DNA, ANF) are detected that are not characteristic of hemorrhagic vasculitis.

Treatment hemorrhagic vasculitis in children.

Indications for hospitalization are the onset and relapse of hemorrhagic vasculitis.

Non-drug treatment of hemorrhagic vasculitis

In the acute period of hemorrhagic vasculitis, hospitalization, bed rest for the period of skin rashes, and a hypoallergenic diet are required. Bed rest is necessary to improve blood circulation until the rash and pain disappear, with subsequent gradual expansion. Violation of bed rest often leads to an increase or repeated rashes. A hypoallergenic diet with the exclusion of obligate allergens (chocolate, coffee, cocoa, citrus fruits - lemons, oranges, grapefruit, tangerines; chicken, chips, carbonated colored drinks, nuts, salted crackers, all red vegetables and fruits) is recommended for all patients in the acute period. In case of severe abdominal pain, table No. 1 (anti-ulcer) is prescribed. In the nephrotic variant of glomerulonephritis, a salt-free diet with protein restriction is used.

Drug treatment of hemorrhagic vasculitis

Drug treatment is carried out taking into account the phase of the disease, clinical form, nature of the main clinical syndromes, severity, and nature of the course.

Severity criteria for hemorrhagic vasculitis:

• mild - satisfactory state of health, minor rashes, arthralgia possible;
• moderate severity - profuse rashes, arthralgia or arthritis, periodic abdominal pain, microhematuria, trace proteinuria;
• severe - profuse, confluent rashes, necrotic elements, angioedema; persistent abdominal pain, gastrointestinal bleeding; macrohematuria, nephrotic syndrome, acute renal failure.

Drug treatment consists of pathogenetic and symptomatic.

Pathogenetic therapy of hemorrhagic vasculitis depends on the nature and duration of the localization of the vascular lesion and its severity. Sodium heparin is used for treatment in an individually selected dose. Antiplatelet agents are prescribed in almost all cases, and fibrinolysis activators are prescribed if indicated. Moreover, if treatment with antiplatelet agents alone is sufficient for a mild course of the disease, then a combination of anticoagulants and antiplatelet agents is necessary for moderate and severe forms. Glucocorticosteroids are prescribed for severe cases of the disease and for Henoch-Schonlein nephritis. Of the drugs with an immunosuppressant effect, cyclophosphamide, azathioprine, and 4-aminoquinoline derivatives are prescribed for nephritis. In the case of acute or exacerbation of chronic foci of infection, antibiotics are used; if the infectious process maintains the recurrence of hemorrhagic vasculitis, immunoglobulins for intravenous administration are included in the treatment complex.

Below are indications for the appointment and methods of using pathogenetic methods of treating hemorrhagic vasculitis.

• Antiplatelet agents - all forms of the disease. Dipyridamole (curantil, persantin) at a dose of 5-8 mg / kg per day in 4 doses; pentoxifylline (trental, agapurin) 5-10 mg / kg per day in 3 doses; ticlopidine (ticlid) 250 mg 2 times a day. In severe cases, two drugs are prescribed simultaneously to enhance the antiplatelet effect. Fibrinolysis activators - nicotinic acid, xanthinol nicotinate (teonikol, complamin) - the dose is selected taking into account individual sensitivity, usually it is 0.3-0.6 g per day. The duration of treatment depends on the clinical form and severity: 2-3 months - in mild cases; 4-6 months - in moderate cases; up to 12 months - in severe recurrent cases and Schonlein-Henoch nephritis; in chronic cases, repeated courses are carried out over a period of 3-6 months.
• Anticoagulants - active period of moderate and severe forms. Sodium heparin or its low-molecular analogue - calcium nadroparin (fraxiparin) are used. The dose of sodium heparin is selected individually depending on the severity of the disease (on average 100-300 U/kg, less often - higher doses), focusing on positive dynamics and coagulogram indicators. In moderate cases, treatment usually lasts up to 25-30 days; in severe cases - until stable relief of clinical syndromes (45-60 days); in hemorrhagic vasculitis nephritis, the duration of heparin therapy is determined individually. The drugs are discontinued gradually by 100 U/kg per day every 1-3 days.
• Glucocorticosteroids - severe course of skin, joint, abdominal syndromes, kidney damage. In simple and mixed form without kidney damage, the oral dose of prednisolone is 0.7-1.5 mg/kg per day for a short course (7-20 days). In the development of Schonlein-Henoch nephritis, 2 mg/kg per day is prescribed for 1-2 months, followed by a decrease of 2.5-5.0 mg once every 5-7 days until cancellation.
• Cytostatics - severe forms of nephritis, skin syndrome with necrosis against the background of high immunological activity. Derivatives of 4-aminoquinoline - when severe symptoms subside against the background of a reduction in the dose of prednisolone or after its cancellation.
• Antibiotics - intercurrent infections at the onset or during the course of the disease, the presence of foci of infection.
• IVIG is a severe, continuously recurring course of the disease associated with bacterial and/or viral infections that are not amenable to treatment. IVIG is administered in low and medium course doses (400-500 mg/kg).

Symptomatic treatment of hemorrhagic vasculitis includes infusion therapy, antihistamines, enterosorbents, NSAIDs. When treating recurrent forms, special attention should be paid to finding a possible cause that supports the pathological process. Most often, these are infectious factors, so sanitizing foci of infection often leads to remission.

In severe cases of hemorrhagic vasculitis in the acute period, intravenous administration of dextran (rheopolyglucin), glucose-novocaine mixture (in a ratio of 3:1) is used. Antihistamines are effective in children with a history of food, drug or household allergies, manifestations of exudative-catarrhal diathesis, allergic diseases (hay fever, Quincke's edema, obstructive bronchitis, bronchial asthma). Clemastine (tavegil), chloropyramine (suprastin), mebhydrolin (diazolin), quifenadine (fenkarol) and other drugs are used in age-related doses for 7-10 days. Enterosorbents [hydrolytic lignin (polyphepan), dioctahedral smectite (smecta), povidone (enterosorb), activated carbon 3-4 times a day for 5-10 days] are necessary for patients with a complicated allergological anamnesis in cases where food agents served as a provoking factor of the disease. Enterosorbents bind toxins and biologically active substances in the intestinal lumen, thereby preventing their penetration into the systemic bloodstream. NSAIDs are prescribed for a short course in case of severe joint syndrome.

Surgical treatment of hemorrhagic vasculitis

Surgical treatment (laparoscopy, laparotomy) is indicated when symptoms of "acute abdomen" develop in a patient with abdominal syndrome. In addition, during the period of remission, according to indications (chronic tonsillitis), tonsillectomy is performed.

Indications for consultation with other specialists

• Surgeon - severe abdominal syndrome.
• ENT, dentist - pathology of ENT organs, need for dental sanitation.
• Nephrologist - Henoch-Schönlein nephritis.

Prevention

Primary prevention of hemorrhagic vasculitis has not been developed. Prevention of exacerbations and relapses of Henoch-Schonlein disease consists of preventing exacerbations, sanitizing foci of infection, refusing to take antibiotics, eliminating contact with allergens, provoking factors - cooling, physical activity, stressful situations.

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Forecast

The outcome of hemorrhagic vasculitis is generally favorable. Recovery after the onset is noted in more than half of patients. A long-term recurrent course of the disease is possible, with the frequency of relapses ranging from single relapses over several years to monthly. With the development of abdominal syndrome, surgical complications are possible (intussusception, intestinal obstruction, intestinal perforation with the development of peritonitis). Schonlein-Henoch nephritis can be complicated by acute renal failure. The prognosis determines the degree of kidney damage, which can result in chronic renal failure. An unfavorable prognosis for hemorrhagic vasculitis is associated with the presence of nephrotic syndrome, arterial hypertension, and extracapillary proliferation in the form of crescents.

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